S-substituted beta-thioacrylamide biocides and fungicides

ABSTRACT

S-substituted beta-thioacrylamide compounds have been discovered to be useful as biocides and fungicides. Compositions comprising the compound and isothiazolin-3-ones and/or carriers, methods of preparation of the compounds and methods of using the compounds and compositions are also disclosed.

This application is a continuation-in-part of serial number 07/387,452 of July 28, 1989.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to biocides and fungicides.

2. Description of the Prior Art

The following references were considered pertinent, but do not describe or suggest the present invention: Miller, et al., U.S. Pat. No. 3,914,301 (Oct. 21, 1975), commonly assigned, and W. D. Crow and I. Gosney, Aust. J. Chem., 22, 765-774 (1969).

SUMMARY OF THE INVENTION

There is a need for alternative biocides and fungicides, especially improved ones.

It is therefore an object of the present invention to provide novel compounds which are useful in any locus subject to contamination by bacteria or fungi.

These objects and others as will become apparent from the following detailed description, are achieved by the present invention which in one aspect comprises a compound of the formula ##STR1## wherein R₁ is selected from unsubstituted or substituted aryl, alkaryl, or aralkyl, Q is ##STR2## wherein W₁ and W₂ are independently selected electron withdrawing groups; and Z₁ and Z₂ are independently selected from hydrogen, halogen and (C₁ -C₄) alkyl.

In another aspect the invention comprises the use of such a compound as a biocide or as a fungicide, and compositions comprising such compounds in fungicidally effective amount and in an agronomically acceptably carrier. In another aspect the invention comprises a method of controlling or inhibiting growth of bacteria in a locus comprising incorporating into or onto the locus a biocidally effective amount of the compound.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTS

The novel compounds of the invention have been found to be useful as bactericides or as fungicides or both. The compounds of the invention have the formula ##STR3## wherein R₁ is an unsubstituted or substituted aryl, alkaryl, or aralkyl group, Q is ##STR4## wherein W₁ and W₂ are independently selected electron withdrawing groups, preferably carbonyl containing groups, and more preferably keto groups, especially acetyl; and Z₁ and Z₂ are independently selected from hydrogen, halogen and (C₁ -C₄) alkyl.

Preferably Z₁ is halogen, especially chlorine and Z₂ is methyl. Q is preferably ##STR5##

R₁ is preferably phenyl or chlorophenyl.

The beta-thioacrylamides of the invention can be used in any locus subject to contamination by bacteria or fungi. Typical loci subject to contamination by bacteria are in aqueous systems such as water cooling, laundry wash water, oil/water systems as cutting oils, oil fields and the like where microorganisms need to be killed or where their growth needs to be controlled.

Specific loci for bacteriostatic and fungistatic application include disinfectants, sanitizers, cleaners, deodorizers, liquid and powder soaps, skin removers, oil and grease removers, food processing chemicals, dairy chemicals, food preservatives, animal food preservatives, wood preservation, paint, lazures, stains, mildewcides, hospital and medical antiseptics, metal working fluids, cooling water, air washers, petroleum production, paper treatment, paper mill slimicides, petroleum products, adhesives, textiles, pigment slurries, latexes, leather and hide treatment, petroleum fuel, jet fuel, laundry sanitizers, agricultural formulations, inks, mining, nonwoven fabrics, petroleum storage, rubber, sugar processing, tobacco, swimming pools, cosmetics, toiletries, pharmaceuticals, chemical toilets, household laundry products, diesel fuel additives, waxes and polishes, electrodeposition systems, diagnostic products, medical devices, water purification systems, filtration systems, fishnets, marine antifoulants and other applications where water and organic materials come in contact under conditions which allow the growth of undesired microorganisms. Solutions of beta-thioacrylamides can also applied to a solid substrate, such as fabric, leather, or wood, as a preservative, or admixed with plastics. It is known in the art that the performance of biocides can frequently be enhanced by combination with one or more other biocides or fungicides. In fact, there have been numerous examples of synergistic combinations of biocides. Thus, other known biocides may be combined advantageously with the beta-thioacrylamides of this invention. See Industrial Antimicrobial Agents Encyclopedia of Chemical Technology, Volume 13, for a list of suitable other biocides. More specific industries and applications for the compounds are:

    ______________________________________                                         Industry       Application                                                     ______________________________________                                         Adhesives, Sealants                                                                           Adhesives                                                                      Caulks                                                                         sealants                                                        agriculture/food chain                                                                        adjuvant preservation                                                          agricultural active ingredient                                                 agricultural chemical preservative                                             agricultural formulations preservation                                         animal feed preservation                                                       dairy chemicals                                                                fertilizer preservation                                                        food preservation                                                              food processing chemicals                                                      grain preservation                                                             post-harvest produce protection                                                sugar processing                                                               tobacco                                                         Construction products                                                                         asphalt/concrete                                                               cement modifiers                                                               construction products                                                          roof mastics                                                                   synthetic stucco                                                               wall mastics                                                                   joint cement                                                    Cosmetics and toiletries                                                                      Cosmetics                                                                      raw materials for cosmetics, toiletries                                        toiletries                                                      Disinfectants, antiseptics                                                                    antiseptic                                                                     disinfectant                                                    Emulsions, dispersions                                                                        aqueous dispersions                                                            dispersed pigments                                                             latex                                                                          photographic emulsions                                                         pigment slurries                                                               polymer latices                                                 formulated household                                                                          fabric softeners                                                products       polishes                                                                       waxes                                                                          hand dish detergents                                                           raw materials                                                                  liquid detergents                                                              hand soaps                                                      Industrial processing, misc                                                                   electrodeposition paint, baths, rinses.                                        electrodeposition pre-treatment, post                                           rinses                                                                        Industrial fluids preservation                                                 pasteurization baths                                                           process aid preservation                                        Industrial water treatment                                                                    air washers                                                                    cooling towers                                                                 cooling water                                                                  water cooling                                                                  preservation/treatment of wooden                                                cooling tower slats and structural                                             members                                                                       can warmers                                                                    brewery pasteurization                                                         closed loop water cooling systems                               Laundry        household laundry products                                                     laundered goods                                                                laundry wash water                                                             sanitizers-laundry                                              Leather, Leather products                                                                     leather and hide                                                               leather and hide products                                       Lubricants, hydraulic aids                                                                    automotive lubricants and fluids                                               conveyor lubricants                                                            greases                                                                        hydraulic fluids                                                               lubricants                                                      Medical devices                                                                               diagnostic enzymes                                                             diagnostic kits                                                                medical devices                                                 metalworking & related                                                                        cutting fluids                                                  app's          Metal cleaning                                                                 metalworking fluids                                             Odor control   air conditioning                                                (active ingredient)                                                                           animal bedding                                                                 cat litter                                                                     chemical toilet prep'ns                                                        deodorizers                                                                    humidifiers                                                                    industrial deodorants                                                          sanitary formulations                                                          toilet bowls                                                    Paints and coatings coating                                                                   emulsions                                                                      paints                                                          Paper and wood pulp,                                                                          abosrbant materials of paper and                                their products  wood pulp                                                                     packaging materials of paper and                                                wood pulp                                                                     paper                                                                          paper products                                                                 paper treatment                                                                soap wrap                                                                      wood pulp                                                                      wood pulp products                                              paper mill     paper mill slimicides                                                          pulp and paper slurries                                         Petroleum refining, fuels                                                                     aviation fuels (jet fuel, aviation gas)                                        crude oils                                                                     burner, diesel and turbine fuel oils                                           coal slurries                                                                  diesel fuel additives                                                          diesel fuels                                                                   fuels                                                                          gasoline                                                                       heating oils                                                                   hydrocarbons                                                                   Kerosene                                                                       liquefied petroleum gas                                                        petrochemical feedstocks                                                       petroleum products, storage,                                                    transportation and production                                                 recycled petroleum products                                                    residual fuel oils                                                             turbine oils                                                    Photographic Chemicals                                                                        Photographic processing - wash                                  and process     water, rinses                                                                 photoprocessing                                                                Photoplate processing chemicals                                                 (developers, stabilizers etc)                                  Printing       Fountain solutions (printing)                                                  Ink components (pigments, resins,                                               solvents, etc)                                                                Inks                                                            sanitizers (active)                                                                           sanitizers                                                                     sanitizers-dairy                                                               sanitizers-dental                                                              sanitizers-fermentation                                                        sanitizers-food preparation                                                    sanitizers-food processing                                                     sanitizers-medical                                                             sanitizers-rendering                                                           sanitizers-veterinary                                           Soaps, detergents, cleaners                                                                   cleaners                                                                       detergents                                                                     household cleaners                                                             industrial cleaners                                                            liquid soaps                                                                   oil and grease remover                                                         powdered soaps                                                                 raw materials for cleaning products                                            soaps                                                                          surfactants                                                     Textiles, textile products                                                                    bonded fabrics                                                                 burlap                                                                         canvas                                                                         canvas goods                                                                   carpet backing                                                                 carpets                                                                        clothing                                                                       coated fabrics                                                                 curtains                                                                       draperies                                                                      engineering textiles                                                           fibers                                                                         geotextiles                                                                    goods made of textiles                                                         knitted fabrics                                                                nets                                                                           nonwoven fabrics                                                               rope                                                                           rugs                                                                           textile accessories                                                            textile products                                                               textiles                                                                       upholstery                                                                     woven fabrics                                                                  yarn                                                            Textile processing                                                                            dye fixatives                                                                  dyes                                                                           fiber lubricants                                                               hand modifiers                                                                 sizes                                                                          Textile processing fluids                                       Therapeutic (active or                                                                        animal health/veterinary                                        preservative)  aquaculture                                                                    dental                                                                         human health                                                                   pharmaceutical/therapeutic                                      water purification                                                                            charcoal beds                                                                  deionization resins                                                            filters                                                                        membranes                                                                      reverse osmosis membranes                                                      ultrafilters                                                                   Water purification                                                             water purification pipes, tubing                                wood applications                                                                             lazures (wood stains)                                                          wood                                                                           wood products                                                   Miscellaneous  alcohols                                                                       bedding incorporating water or gels                                            ceramic                                                                        contact lens cases-leaching                                                    electronic circuitry                                                           electronics chemicals                                                          enzymes-food production                                                        enzymes                                                                        enzymes-industrial                                                             gel cushions                                                                   marine antifoulants                                                            mildewcides                                                                    wood                                                                           plastics                                                                       laundry                                                                        mining                                                                         natural rubber latex                                                           oil field injection waters including                                            enhanced recover injection fluids,                                             drilling, fracturing and completion                                            fluids                                                                        pipes                                                                          plastics                                                                       polymer systems                                                                polymers and resins (synthetic and                                              natural)                                                                      reagent preservation                                                           rubber                                                                         rubber products                                                                skin remover                                                                   solid protective/decorative films                                              stains                                                                         swimming pools                                                                 waste treatment                                                                water beds                                                      ______________________________________                                    

The beta-thioacrylamide compounds of the invention can be applied as fungicidal sprays by methods commonly employed, such as conventional high-gallonage hydraulic sprays, low-gallonage sprays, airblast, aerial sprays and dusts. The dilution and rate of application will depend upon the type of equipment employed, the method and frequency of application desired and diseases to be controlled, but the effective amount for application is usually from about 5 grams (gm) to about 22 kilograms (kg), preferably from about 0.010 to about 1.0 kg per hectare.

As a seed protectant, the amount of fungicide coated on the seed is usually at a dosage rate of about 0.0001 to about 10 grams (gm) and preferably from about 0.1 to about 10 gm per 1 kilogram of seed. As a soil fungicide the beta-thioacrylamides can be incorporated in the soil or applied to the surface usually at a rate of 0.01 to about 22 kg, preferably about 0.05 to about 11 kg and more preferably from about 0.1 to about 3.3 kg per hectare. As a foliar fungicide the beta-thioacrylamides can be applied at a rate of from about 0.01 to about 11 kg, preferably from about 0.02 to about 5.5 kg and more preferably from about 0.1 to about 3.3 kg per hectare.

The present invention is useful for the control of fungi and can be utilized at various loci such as the seed, the soil or the foliage. For such purposes these compounds can be used in the technical or pure form as prepared, as solutions or as formulations. The compounds are usually taken up in a carrier or are formulated so as to render them suitable for subsequent dissemination as fungicides. For example, these beta-thioacrylamides can be formulated as wettable powders, emulsifiable concentrates, dusts, granular formulations, aerosols, or flowable emulsion concentrates. In such formulations, the beta-thioacrylamides are extended with a liquid or solid carrier and, when desired, suitable surfactants are incorporated.

It is usually desirable, particularly in the case of foliar spray formulations, to include adjuvants, such as wetting agents, spreading agents, dispersing agents, stickers, adhesives and the like in accordance with agricultural practices. Such adjuvants commonly used in the art can be found in McCutcheon's Emulsifiers and Detergents, McCutcheon's Emulsifiers and Detergents/Functional Materials and McCutcheon's Functional Materials all published annually by McCutcheon Division of MC Publishing Company (New Jersey). In general, the beta-thioacrylamides of this invention can be dissolved in appropriate solvents such as acetone, methanol, ethanol, dimethylformamide or dimethyl sulfoxide and such solutions extended with water. The concentrations of the solution can vary from 1% to 90% with a preferred range being 5 to 50% (weight percentage). For the preparation of emulsifiable concentrates, the beta-thioacrylamides can be dissolved in suitable organic solvents or a mixture of solvents, together with an emulsifying agent which permits dispersion of the fungicide in water. The concentration of the active ingredient in emulsifiable concentrates is usually 10% to 90% and in flowable emulsion concentrates, this can be as high as 75% (weight percent). Water based flowable formulations of the beta-thioacrylamides can be prepared with a concentration of active ingredients in the range of 5 to 70% by weight, preferably 20 to 50% by weight.

A typical flowable formulation is prepared by wet-milling a mixture of 35 parts of beta-thioacrylamides, 10 parts of Barden clay, 4 parts of sodium lignosulfonate, 1 part of an anionic wetting agent and 50 parts of water.

Wettable powders suitable for spraying can be prepared by admixing the beta-thioacrylamide compound with a finely divided solid, such as clays, inorganic silicates and carbonates, and silicas and incorporating wetting agents, sticking agents, and/or dispersing agents in such mixtures. The concentration of active ingredients in such formulations is usually in the range of 5% to 98%, preferably 40% to 75% (weight percent), optional by blending 50 parts of an active ingredient selected from the S-substituted beta-thioacrylamides of Examples 1-7, 45 parts of a synthetic precipitated hydrated silicon dioxide sold under the trademark Hi-Sil, 1 part of an anionic naphthalenic sulfonate wetting agent and 4 parts of sodium lignosulfonate (Marasperse N-22). In another preparation of a kaolin type (Barden) clay is used in place of the Hi-Sil in the above wettable powder and in another such preparation 25% of the Hi-Sil is replaced with a synthetic sodium silico aluminate sold under the trademark Zeolex 7. Dusts are prepared by mixing the amides and salts and complexes thereof with finely divided inert solids which can be organic or inorganic in nature. Materials useful for this purpose include botanical flours, silicas, silicates, carbonates, talc and clays. One convenient method of preparing a dust is to dilute a wettable powder with a finely divided carrier. Dust concentrates containing 20% to 80% (weight percent) of the active ingredient are commonly made and are subsequently diluted to 1% to 10% use concentration.

The compounds of the present invention may also be utilized in combination with other fungicides such as:

(a) dithiocarbamates and derivatives such as: ferric dimethyldithiocarbamate (ferbam), zinc dimethyldithiocarbamate (ziram), manganese ethylenebisdithiocarbamate (maneb) and its coordination product with zinc ion (mancozeb), zinc ethylenebisdithiocarbamate (zineb), zinc propylenebisdithiocarbamate (propineb), sodium methyldithiocarbamate (metham), tetramethylthiuram disulfide (thiram), the complex of zineb and polyethylene thiuram disulfide, 3,5-dimethyl-1,3,5-2H-tetrahydrothiadiazine-2-thione (dazomet); and mixtures of these and mixtures with copper salts;

(b) nitrophenol derivatives such as: dinitro-(1-methylheptyl)phenyl crotonate (dinocap), 2-sec-butyl-4,6-dinitrophenyl-3,3-dimethylacrylate (binapacryl), and 2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate;

(c) heterocyclic structures such as: Systhane (a registered trademark of Rohm and Haas for myclobutanil), triademifon, N-trichloromethylthiotetrahydrophthalimide (captan), N-trichloromethylthiophthalimide (folpet), 2-heptadecyl-2-imidazole acetate (glyodine), 2-octylisothiazolone-3, 2,4-dichloro-6-(o-chloroanilino)-s-triazine, diethyl phthalimidophosphorothioate, 4-butyl-1,2,4-triazole, 5-amino-1-[bis(dimethylamino)phosphinyl]-3-phenyl-1,2,4-triazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, 2,3-dicyano-1,4-dithiaanthraquinone (dithianon), 1,3-dithiolo-[4,5-b]quinoxaline-2-thione (thioquinox), methyl 1-(butylcarbamoyl)-2benzimidazole carbamate (benomyl), 2,4'-(thiazolyl) benzimidazole (thiabendazole), 4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione (vinclozolin), 3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-di-alphaoxo-1-imidazolinecarboxamide (dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide (procymidone), beta-(4-chlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-trizole-1-ethanol (triadimenol), 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone (triadimefon), beta-[(1,1'-biphenyl)-4-yloxy]-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1ethanol (bitertanol), 2,3-dichloro-N-(4-fluorophenyl)maleimide (fluoroimide), 1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-triazole, pyridine-2-thiol-1-oxide, 8-hydroxyquinoline sulfate and metal salts thereof, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin-4,4-dioxide, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin, alpha-(phenyl)-alpha-(2,14-dichlorophenyl)-5-pyrimidinyl-methanol (triarimol), cis-N[(1,1,2,2-tetrachloroethyl)thio]-4-cyclohexene-1,2-dicarboximide, 3-[2-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxy]-glutarimide (cycloheximide), dehydroacetic acid, N-(1,1,2,2-tetrachloroethylthio)-3a,4,7,7a-tetrahydrophthalimide (captafol), 5-butyl-2-ethylamino-4-hydroxy-6-methyl-pyrimidine (ethirimol), acetate of 4-cyclodecyl-2,6-dimethyl-morpholine (dodemorph), and 6-methyl-2-oxo-1,3-dithiolo[4,5-b]-quinoxaline (quinomethionate);

(d) miscellaneous halogenated fungicides such as: tetrachloro-p-benzoquinone (chloranil), 2-3-dichloro-1,4-naphthoquinone (dichlone), 1,4-dichloro-2,5-dimethoxybenzene (chlorneb), 3,5,6-trichloro-o-anisic acid (tricamba), 2,4,5,6-tetrachloroisophthalonitril (TCPN), 2,6-dichloro-4-nitroaniline (dichloran), 2-chloro-1-nitropropane, polychloronitrobenzenes such as: pentachloronitrobenzene (PCNB) and tetrafluorodichloroacetone;

(e) fungicidal antibiotics such as: griseofulvin, kasugamycin and streptomycin;

(f) copper-based fungicides such as: copper hydroxide, cuprous oxide, basic cupric chloride, basic copper carbonate, copper terphthalate, copper naphthenate and Bordeaux mixture; and

(g) miscellaneous fungicides such as: diphenyl, sultone, dodecylguanidine acetate (dodine), phenylmercuric acetate, N-ethylmercuri-1,2,3,6-tetrahydro-3,6-endomethano-3,4,5,6,7,7-hexachlorophth alimide, p-dimethylaminobenzene sodium sulfonate, methyl isothiocyanate, 1-thiocyano-2,4-dinitrobenzene, 1-phenylthiosemicarbazide, nickel-containing compounds, calcium cyanamide, lime sulfur, 1,2-bis(3-methoxycarbonyl-2-thioureido) benzene (thiophanate-methyl).

All of the novel S-substituted beta-thioacrylamides of the invention can be prepared by reacting an unsubstituted or substituted 4-isothiazolin-3-one with a suitable nucleophilic reagent. This reaction can be schematically represented as follows: ##STR6## in which QH represents a typical nucleophilic reagent, for which Q is defined as: ##STR7## wherein W₁ and W₂ are independently selected electron withdrawing groups, R₁ is an unsubstituted or substituted aryl, alkaryl, or aralkyl group, and Z₁ and Z₂ are independently selected from hydrogen, halogen, and (C₁ -C₄)alkyl groups. A preferred nucleophilic agent which can be used to cleave the 4-isothiazolin-3-one ring is a beta-diketone, especially 2,4-pentanedione.

In preparing the compounds of the invention, equimolar amounts of the 4-isothiazolin-3-one and the nucleophilic reagent are generally used. The convenient in-situ formation of sodium ethoxide from sodium metal in absolute ethanol can be advantageously used to facilitate the reaction between the 4-isothiazolin-3-one and the nucleophilic reagent by allowing the abstraction of the proton from the Q-H nucleophilic reagent to take place. The reaction between the nucleophilic reagent and the 4-isothiazolin-3-one is generally carried out at a temperature of about 0° C. to about 100° C., and preferably below 30° C. in that range. Various organic solvents can be used in carrying out the reaction, if desired, with an alcoholic solvent being preferred. However, any solvent or mixture of solvents which will not interfere with the reaction can be used. Under high pH conditions this reaction is reversable, resulting in compositions comprising both the compounds and the 4-isothiazolin-3-one percurser.

All of the 4-isothiazolin-3-one intermediates can be prepared by the cyclization of a substituted disulfidediamide having the formula: ##STR8## wherein Y₁ and Y₂ are hydrogen or (C₁ -C₄)alkyl groups and R₁ is defined as above. The cyclization is accomplished by reacting the disulfidediamide with a halogenating agent. Any halogenating agent can be employed in this reaction, with chlorine and sulfuryl chloride being preferred. Cyclization of the disulfidediamide will take place when 3 mole equivalents of halogenating agent/mole equivalent of disulfidediamide are employed in the reaction. By providing an excess of halogenating agent, the 4-isothiazolin-3-one may be halogenated at the 4- and/or 5-positions of the ring. Where 5 mole equivalents of halogenating agent are available, mono-halogenation can take place. For dihalogenation, 7 mole equivalents of halogenating agent are required. The cyclization process will proceed over a broad temperature range and temperature is not critical to the reaction. Generally, the cyclization will be carried out in the range of -10° C. to 100° C. The reaction is carried out in an inert non-aqueous solvent, such as ethyl acetate, ethylene dichloride, benzene, toluene, or xylene.

The following examples will further illustrate this invention, but are not intended to limit it in any way. All parts and percentages are by weight and all temperatures in degrees Centigrade, unless otherwise stated.

EXAMPLES EXAMPLE 1 Synthesis of N-(p-Chlorophenyl)-2-methyl-3-chloro-cis-3-thio-(1-acetylpropan-2-on-1-yl) acrylamide

A. To a 500 ml, 4-neck flask equipped with a mechanical stirrer, addition funnel, and a thermometer was placed 80 ml of ethyl acetate which was cooled to 0° C. Concurrently, 12.0 g (0.026 mol) of N,N'-bis-(p-chlorophenyl)-3,3'-dithiodiisobutyramide and 17.7 g (0.131 mol) of sulfuryl chloride then were added, both in 24 equal portions with stirring over a one hour period. After allowing the resulting mixture to warm to room temperature, the yellowish solution was concentrated under reduced pressure. The solid residue was recrystallized from 2-propanol to give 6.1 g (89% yield) of 2-(p-chlorophenyl)-4-methyl-5-chloro-4-isothiazolin-3-one intermediate as white needles whose m.p.=104.5°-106° C.

B. To a dry, nitrogen purged 500 ml three-necked flask, equipped with a condenser, magnetic stirring bar, and a thermometer was added 75 ml of absolute ethanol. Freshly cut sodium metal (0.53 gm, 0.023 mol) was added in pieces with stirring at such a rate that the temperature of the mixture remained below 35° C. When all the sodium had dissolved, 2.31 gm (0.023 mol) of 2,4-pentanedione was added dropwise over a ten minute period with stirring. After allowing the solution to stir for 15 minutes, 6.0 gm (0.023 mol) of 2-(p-chlorophenyl)-4-methyl-5-chloro-4-isothiazolin-3-one in 60 ml of warm absolute ethanol was added over 20 minutes, keeping the temperature of the reaction mixture below 30° C. The mixture was stirred for an additional one hour and then poured into an ice-cold, 2N HCl solution with stirring. The solid precipitate was removed by filtration and washed three times with fresh water. The solid was dried under vacuum at 40° C. to give 7.8 gm (93.5% yield) of product which recrystallized from absolute ethanol as white, cottony needles; mp 164°-166° C.; IR (KBr): 3300 cm⁻¹ (NH), 1660 cm⁻¹ (C═O); NMR (CDCl₃): 2.2 ppm (s,CH₃), 2.4 ppm (s,2CH₃), 7.2-7.6 ppm (m, 5H, aromatic and NH), 17.3 ppm (s, CH). Melting point was 164°-166° C.

EXAMPLES 2-7

In a like manner other compounds having the general formula ##STR9## were prepared, wherein R₁,Q,Z₁ and Z₂, for each compound were as shown in Table 1, and were identified as indicated in said Table 1.

The intermediates for Examples 2-7 were prepared as follows:

A. Preparation of 2-Benzyl-4-isothiazolin-3-one Intermediate for Example 2

To a suspension of 58.2 g (0.15 mol) of N,N'-bis-benzyl-3,3'-dithiodipropionamide in 500 ml of ethylene dichloride at 10-15° C. was added dropwise 63.6 g (0.473 mol) of sulfuryl chloride. A clear, light amber solution resulted. After stirring overnight, the solution was concentrated to give about one half volume. Cream-colored solid separated and was collected by filtration, yielding 36.1 g of 2-benzyl-4-isothiazolin-3-one hydrochloride salt; 1.5 g of additional solid separated in the filtrate but proved to be starting material. The filtrate was further evaporated to a brown oil. The oil was redissolved in benzene, treated with decolorizing carbon, and evaporated once again. The resulting light amber oil solidified on standing. This light tan solid was recrystallized from heptane giving 8.0 g(12% yield) of white crystals of 2-benzyl-5-chloro-4-isothiazolin-3-one hydrochloride salt whose m.p. was 58°-59° C. The hydrochloride of the unchlorinated benzyl compound was converted to free base by trituration with water and was dried under vacuum to give 27.0 g (47% yield) of the 2-benzyl-4-isothiazolin-3-one intermediate, m.p.=78°-80° C.

B. Preparation of 2-(Beta-phenethyl)-4-isothiazolin-3-one Intermediate for Example 3

To a slurry of 103.9 g (0.25 mol) of N,N'-bis-(beta-phenethyl)-3,3'-dithiodipropionamide in 1000 ml of ethylene dichloride at 10-15° C. was added 101.3 g (0.75 mol) of sulfuryl chloride over a one hour period. After the addition, the mixture was allowed to warm to room temperature. The yellowish slurry mixture was concentrated to remove about two-thirds of the ethylene dichloride and the separated solid mass was removed by filtration and washed with ether. The solid was added to a mixture of 350 ml of water and 200 ml of chloroform. Solid sodium bicarbonate was added in portions with stirring until the aqueous phase was at pH 7-8. The layers were separated and the aqueous phase extracted with additional chloroform. The combined chloroform layers were dried over magnesium sulfate and concentrated to give a white solid residue which was recrystallized from a benzene/hexane mixture to give 44.8 g (44% yield) of the 2-(beta-phenethyl)-4-isothiazolin-3-one intermediate whose m.p. was 76°-78° C.

C. Preparation of 2-(p-Chlorobenzyl)-4-isothiazolin -3-one Intermediate for Example 4

To a slurry of 292.0 g (0.639 mol) of N,N'-bis-(4-chlorobenzyl)-3,3'-dithiodipropionamide in 2 liters of ethyl acetate was added 136.0 g (1.9717 mole) of chlorine in one hour, during which the reaction temperature rose to 47° C. The mixture was allowed to cool to room temperature, degassed, and then cooled to 10° C. The solid was removed by filtration, triturated with 200 ml of water, filtered, and dried. The dried solid was dissolved in 500 ml of boiling ethyl acetate and filtered to remove unreacted amide starting material. The ethyl acetate solution, on cooling, deposited a crystalline solid which was filtered and dried to give 132.2 g (46% yield) of the 2-(p-chlorobenzyl)-4-isothiazolin-3-one intermediate with a m.p.=88°-90° C.

D. Preparation of 2-Phenyl-4-methyl-5-chloro-4-isothiazolin-3-one Intermediate for

Example 5

To 400 ml of ethyl acetate at 0° C. was added, during a one hour period, 155.2 g (0.4 mol) of N,N'-bis-phenyl-3,3'-dithiodiisobutyramide in 40 equal portions and 116.5 g (1.64 mol) of chlorine. The temperature was maintained at 0°-5° C. during the additions. The mixture was then allowed to warm to 15° C. The solution was then evaporated under reduced pressure, leaving a brown oil which partially solidified on standing. This material was dissolved in warm ethanol. On cooling, pink solid separated which was removed by filtration. The filtrate was evaporated to a dark oil. The oil was extracted with ether. Evaporation of the ether gave 112.7 g of a yellow mush. Three grams of this mush was chromatographed on a silica dry column developed with toluene. The main fraction (1.92 g), with a R value of approximately 0.7, was extracted from the silica with ether which was then evaporated. On standing, the residual oil solidified. This material was recrystallized from ethanol to give the cream-colored 2-phenyl-4-methyl-5-chloro-4-isothiazolin-3-one intermediate whose m.p.=60°-68° C.

E. Preparation of 2-(p-Chlorophenyl)-5-chloro-4-isothiazolin-3-one Intermediate for

Example 6

To a suspension of 21 g (0.05 mol) of N,N'-bis-(p-chlorophenyl)-3,3'-dithiodipropionamide in 75 ml of ethyl acetate at 15° C. was added 18.6 g (0.26 mol) of chlorine over a 30 minute period. When addition was complete, the mixture was allowed to stand for several hours and then filtered. The collected solid was triturated with methanol and yielded a white solid. This material was crystallized from 140 ml of toluene with decolorization, using activated carbon, to give 5.82 g (19.5% yield) of the 2-(p-chlorophenyl)-5-chloro-4-isothiazolin-3-one intermediate whose m.p.=117°-119° C.

F. Preparation of 2-(p-Chlorophenyl)-4-methyl-4-isothiazolin-3-one Intermediate for Example 7

In a 2-liter flask equipped with a mechanical stirrer, two addition funnels, and a thermometer was placed one liter of ethyl acetate which was cooled to -5° to 0° C. Concurrently, N,N,'-bis-(p-chlorophenyl)-3,3'-dithiodiisobutyramide (116.3 g, 0.254 mol), sulfuryl chloride (141.7 g, 105 mol), and pyridine (40.0 g, 0.05 mol) were added over a 75 minute period while maintaining the temperature at 0° C. The mixture was allowed to warm to room temperature and then cooled back to -40° C. using a dry-ice bath. The solid precipitate was removed by filtration, washed with cold ethyl acetate, triturated with one liter of water, refiltered, and dried to give 46 g of 2-(p-chlorophenyl)-4-methyl-4-isothiazolin-3-one and 2-(p-chlorophenyl)-4-methyl-5-chloro-4-isothiazolin-3-one in a 2/1 mixture ratio. The dried solid mixture, 45.5 g, and sulfuryl chloride, 19.0 g (0.135 mol) were added concurrently to 300 ml of ethyl acetate at 0° C. over a one hour period. After the addition, the mixture was allowed to warm to room temperature and stirred overnight. The solid suspension was removed by filtration and treated with sodium bicarbonate solution. The treated solid was removed, dried, and recrystallized from 2-propanol to give 9.5 g of 2-(p-chlorophenyl)-4-methyl-4-isothiazolin-3-one intermediate whose m.p.=157°-159° C.

                                      TABLE 1                                      __________________________________________________________________________     Substituents and M.P.'s for Examples 2-7                                       Example                                                                             Melting Point (°C.)                                                               R.sub.1      Z.sub.1                                                                           Z.sub.2                                                                            O                                           __________________________________________________________________________     2    143.5-145 CH.sub.2 φ                                                                              H  H   CH(COCH.sub.3).sub.2                        3    136-139   CH.sub.2 CH.sub.2 φ                                                                     H  H   CH(COCH.sub.3).sub.2                        4    134-137                                                                                   ##STR10##   H  H   CH(COCH.sub.3).sub.2                        5    107-112   φ        Cl CH.sub.3                                                                           CH(COCH.sub.3).sub.2                        6    164-166                                                                                   ##STR11##   Cl H   CH(COCH.sub.3).sub.2                        7    120-125                                                                                   ##STR12##   H  CH.sub.3                                                                           CH(COCH.sub.3).sub.2                        __________________________________________________________________________

                  TABLE 2                                                          ______________________________________                                         Starting Materials for Examples 2- 7                                           Example  Starting Isothiazolone                                                ______________________________________                                         2        2-benzyl-4-isothiazolin-3-one                                         3        2-(beta-phenethyl)-4-isothiazolin-3-one                               4        2-(p-chlorobenzyl)-4-isothiazolin-3-one                               5        2-phenyl-4-methyl-5-chloro-4-isothiazolin-3-one                       6        2-(p-chlorophenyl)-5-chloro-4-isothiazolin-3-one                      7        2-(p-chlorophenyl)-4-methyl-4-isothiazolin-3-one                      ______________________________________                                    

                                      TABLE 3                                      __________________________________________________________________________     Names of Compounds of Examples 2-7                                             Example                                                                             Compound                                                                  __________________________________________________________________________     2    N-benzyl-cis-3-thio-(1-acetylpropan-2-on-1-yl)acrylamide                  3    N-(beta-phenethyl)-cis-3-thio-(1-acetylpropan-2-on-1-yl)-                      acrylamide                                                                4    N-(p-chlorobenzyl)-cis-3-thio-(1-acetylpropan-2-on-1-yl)-                      acrylamide                                                                5    N-phenyl-2-methyl-3-chloro-cis-3-thio-(1-acetylpropan-2-                       on-1-yl)acrylamide                                                        6    N-(p-chlorophenyl)-3-chloro-cis-3-thio-(1-acetylpropan-                        2-on-1-yl)acrylamide                                                      7    N-(p-chlorophenyl)-2-methyl-cis-3-thio-(1-acetylpropan-                        2-on-1-yl)acrylamide                                                      __________________________________________________________________________

                  TABLE 4                                                          ______________________________________                                         Substituents for Examples 8-13                                                  ##STR13##                                                                     Example                                                                               R.sub.1       Z.sub.1                                                                               Z.sub.2                                                                              Q                                            ______________________________________                                                 ##STR14##    Cl     CH.sub.3                                                                             CH(COCH.sub.3).sub.2                         9                                                                                      ##STR15##    Cl     Cl    CH(COCH.sub.3).sub.2                         10                                                                                     ##STR16##    Cl     CH.sub.3                                                                             CH(COCH.sub.3).sub.2                         ______________________________________                                    

                  TABLE 5                                                          ______________________________________                                         Names of Compounds of Examples 8- 10                                           Example  Compound                                                              ______________________________________                                         8        N-(p-tolyl)-2-methyl-3-chloro-cis-3-thio-                                      (1-acetylpropan-2-on-1-yl) acrylamide                                 9        N-[beta-(o-ethylphenethyl)]-2,3-dichloro-cis-3-thio-                           (1-acetylpropan-2-on-1-yl)acrylamide                                  10       N-(m-methylbenzyl)-2-methyl-3-chloro-cis-3-thio-                               (1-acetylpropan-2-on-1-yl)acrylamide                                  ______________________________________                                    

EXAMPLE 11 Biocidal Activity of Compounds

The compounds of Examples 1 and 5 were subjected to the following biocidal activity test procedures, with the results as indicated in Table 6.

The Speed of Kill (SOK) Test measures the loss of cell viability in an aqueous suspension of bacterial cells during a four hour period when these cells are contacted with a defined concentration of the test compound in synthetic hard water (SHW). A stock solution or dispersion of the test compound, typically at a concentration of 1%, is made in a 5:3:2 solvent solution of acetone, methanol, and water. The SHW is made by taking one liter of sterile deionized water and adding the following solutions to it:

1. 2 ml of a solution of 31.74 g of MgCl₂ and 73.99 g of CaCl₂ in 1000 ml. of sterile distilled water which has been heat sterilized.

2. 4 ml of a solution of 56.03 g of NaHCO₃ in 1000 ml of water which has been filter sterilized.

The combined solution is then filter sterilized to yield the SHW. A volume of the stock solution is dispensed into the SHW to give an initial test compound starting concentration of 500 ppm.

When the test is ready to be run, each vessel in the dilution series, except the first vessel, contains an equal volume of the SHW mixture with the test compound. The first vessel contains twice the volume of SHW with the starting concentration of test compound. One half of the SHW from the first vessel is transferred to the second vessel. After being mixed, one half the resulting volume is removed from the second vessel and transferred to the third vessel. The entire cycle is repeated sufficiently to give a series of concentrations amounting to 500, 250, 125, 63, 31, 16, 8, and 4 ppm, respectively.

Each vessel is then inoculated with a cell suspension of Pseudomonas fluorescens bacteria. The bacteria were grown on a 1% agar slant tube and incubated for 18-24 hours at 30° C. Thereafter, the tube is washed with 4 ml of sterile water. This wash is diluted to a density of 60 to 80 Nephelometer Turbidity Units (NTU). To 100 ml of the SHW containing the various concentrations of the test compound is added 0.75 ml of inoculum from the 60-80 NTU wash with good mixing. After 4 hours from the time of addition at 30° C., 5 μl of solution is transferred to 100 μl of a broth solution in order to recover any living cells. This mixture is incubated for 24 hours at 30° C. before noting the concentration in ppm at which each compound killed >99.999% of the cells in the SHW solution.

A minimum inhibitory concentration (MIC) value is obtained using a broth, two-fold serial dilution test performed as follows: A stock solution or dispersion of the test compound, typically at a concentration of 1%, is made in a 5:3:2 solvent solution of acetone, methanol, and water. A volume of the stock solution is dispensed into culture media to give an initial starting test concentration of 500 ppm compound.

When the test is ready to be done, each vessel in the dilution series, except the first vessel, contains an equal volume of compound free broth. The first vessel contains twice the volume of broth with the starting concentration of test compound. One half of the broth from the first vessel is transferred to the second vessel. After being mixed, one half the resulting volume is removed from the second vessel and transferred to the third vessel. The entire cycle is repeated sufficiently to give a series of concentrations amounting to 500, 250, 125, 63, 31, 16, 8, and 4 ppm, respectively.

Each vessel is then inoculated with a cell suspension of the appropriate test organism. Bacteria are grown in broth and fungi on agar slants for a time and at a temperature appropriate to the species being tested. At the end of the growth period, the broth is vortexed to disperse the cells. In the case of fungi, the spores are harvested by pipetting water onto the slant and dislodging the spores with a sterile loop. The cell/spore suspension is standardized by controlling incubation time, temperature, and the volume of the diluent. The suspension is then used to inoculate the vessels containing the broth compound. The vessels are then incubated at the appropriate temperature. After the incubation, the vessels are examined for growth/no growth. The minimum inhibitory concentration (MIC) is defined as the lowest concentration of compound that results in complete inhibition of growth of the test organism.

The organisms tested to demonstrate biocidal activity include:

BACTERIA:

Pseudomonas fluorescens (Ps.fl), gram negative

Pseudomonas aerugenosa (Ps.ae), gram negative

Escherichia coli (E.c), gram negative

Staphylococcus aureus (S.a), gram positive

FUNGI:

Aspergillus niger (A.n)

Aureobasidium pullulans (A.p)

                  TABLE 6                                                          ______________________________________                                         SOK and MIC Test Results in Ppm                                                Example SOK    Ps.fl   PS.ae E.c   S.a  A.n   A.p                              ______________________________________                                         1        32    <4      <4    <4    <4   <4    <4                               5       <4     <4       8    <4    <4   <4     32                              ______________________________________                                    

The compounds of Examples 1-7 were subjected also to the following alternate biocidal activity test procedures, with the results as indicated in Table 7.

SPEED OF KILL TEST

The SOK test measures the viability of Pseudomonas fluorescens inoculum in synthetic hard water (SHW) when exposed for 24 hours to a 100 ppm acetone solution of a given compound.

An acetone solution of the compound was prepared at 10,000 ppm and 0.1 ml was added to 9.8 ml of SHW. 0.1 ml of Ps fl inoculum at 10,000,000 cells per ml was added to the SHW, providing 10 ml of solution which was incubated for 24 hours prior to recovery into Tryptic Soy Broth (TSB).

To recover and measure the living cells, 2.5 ml of the SHW mix was transferred to a reservoir from which 2.5 μl was then transferred 8 times to microtiter wells containing 225 μl of TSB. Each of the 8 transfers was then serially diluted seven times, providing eight replicates of eight dilutions. The concentration at which no living cells were recovered was used to back calculate the log reduction. The data was entered into the database, and the log reductions calculated automatically.

MINIMUM INHIBITORY CONCENTRATION TEST

The MIC test measures the viability of Pseudomonas fluorescens inoculum in TSB when exposed for 72 hours to varying concentrations of test compound.

A 125 μl aliquot of 10,000 ppm test compound in acetone was added to 4.88 ml of TSB to provide a 250 ppm solution. From this solution, 100 μl was transferred to the first row of two microtiter plate columns. Both replicates and five additional compounds were all serially diluted 1:1 to a final concentration of 0.8 ppm in TSB.

Inoculation was accomplished by diluting a 24 hr Ps fl culture, four mls per 36 mls of phosphate buffer solution. A Dynatech autoinoculator was used to transfer 1.5 μl of this cell suspension to the microtiter plates. The plates were incubated at 30° C. for 3 days before the lowest concentration at which no growth occurs was recorded in the database.

The SOK data and MIC test data on Ps.fl, Ps.ae, E.c, and S.a bacteria and Candida albicans (C.alb), A.n and A.p fungi are listed in Table 8.

                                      TABLE 7                                      __________________________________________________________________________     SOK and MIC Test Results in Ppm                                                Compound of Ex.                                                                         SOK A.n  A.p                                                                               C.alb                                                                              E.c Ps.ae                                                                              Ps.fl                                                                              S.a                                       __________________________________________________________________________     1        1-100                                                                              4-8  <4 <4  <4    8 4-16                                                                               <4                                        2         100                                                                               125-500                                                                             31 31-63                                                                              63-125                                                                              500                                                                               >500                                                                               31                                        3         100                                                                                63-500                                                                             8-16                                                                              31  250 >500                                                                               >500                                                                               63                                        4        >100                                                                                31-500                                                                             16 63  63  >500                                                                               >500                                                                               31                                        5        >100                                                                               <4   16 16  <4  16-31                                                                                16                                                                                8                                        6        >100                                                                               >500 *  *   *   *   >500                                                                               *                                         7        >100                                                                               31-63                                                                               4-8                                                                               16  63-125                                                                             >500                                                                               >500                                                                               125                                       __________________________________________________________________________      *Test not run.                                                           

EXAMPLE 12

The compounds of Examples 1 to 7 were subjected to the following fungicides test with the results as indicated in Table 8.

DESCRIPTION OF FUNGICIDE TEST METHODS

The compounds of Examples 1 to 7 were tested for fungicidal activity in vivo against cucumber downy mildew (CDM), rice blast (RB), rice sheath blight (RSB), tomato late blight (TLB), wheat powdery mildew (WPM), wheat stem rust (WSR) and wheat leaf rust (WLR). In tests on cereals (except for rice plants used for testing rice blast), the plants were trimmed about 24 hours prior to the application of the fungicide compound to provide a uniform plant height and to facilitate uniform application of the compound and inoculation with the fungus. The compounds were dissolved in a 2:1:1 mixture of water, acetone, and methanol, sprayed onto the plants, allowed to dry (four to six hours), and then the plants were inoculated with the fungus. Each test utilized control plants which were sprayed with the water, acetone, and methanol mixture and inoculated with the fungus. The remainder of the technique of each of the tests is given below and the results are reported as percent disease control (percentages of plants treated with the compounds of the present invention lacking disease signs or symptoms compared to the untreated control plants).

CUCUMBER DOWNY MILDEW (CDM)

Pseudoperonospora cubensis was maintained on leaves of live Marketer cucumber plants in a constant temperature room at 65° F. to 75° F. in humid air with moderate light intensity for 7 to 8 days. A water suspension of the spores from infested leaves was obtained and the spore concentration was adjusted to about 100,000 per ml of water. Marketer cucumber seedlings were inoculated by spraying the underside of the leaves with a DeVibiss atomizer until small droplets were observed on the leaves. The inoculated plants were incubated in a mist chamber for 24 hours at about 70° F. and then subsequently incubated for 6 to 7 days in a controlled temperature room under mist at 65° F. to 75° F. Seven days after inoculation, the percent disease control was determined.

RICE BLAST (RB)

Nato rice plants were inoculated with Piricularia oryzae (about 20,000 conidia per ml) by spraying the leaves and stems with an airbrush until a uniform film of inoculum was observed on the leaves. The inoculated plants were incubated in a humid environment (75° F. to 85° F.) for about 24 hours, then placed in a greenhouse environment (70° F. to 75° F.). Seven to eight days after inoculation, the percent disease control was determined.

RICE SHEATH BLIGHT (RSB)

Pellicularia filamentosa (f. sp. sasiki) was cultured on an autoclaved mixture of crushed rice seeds and potato dextrose broth (100 gm of rice seeds per 30 ml of potato dextrose broth) in a 500 ml Erlenmeyer flask. After 10 days, the culture was blended in a blender to produce a uniform inoculum. Approximately one teaspoon of inoculum was spread among Lebonnet rice seedlings on the soil surface of each pot (3 inch diameter). The inoculated seedlings were incubated for 5 days in a humidity cabinet (85° F. to 90° F.). Percent disease controls were determined immediately after removing the seedlings from the cabinet.

TOMATO LATE BLIGHT (TLB)

Phytophthora infestans was cultured on four week old Pixie tomato plants in a controlled environment room (65° F. to 70° F. and 100% relative humidity). After storage, the spores were washed from the leaves with water and dispersed by DeVilbiss atomizer over three week old Pixie tomato plants which had been sprayed previously with experimental fungicides. The inoculated plants were placed in a humidity cabinet at 70° F. and constant mist for 24 hours for infection. The plants were then moved to the controlled environment room as above and scored after three more days incubation. Disease control levels were recorded as percent control four days after inoculation and five days after spraying the compounds.

WHEAT POWDERY MILDEW (WPM)

Erysiphe graminis (f. sp. tritici) was cultured on Pennol wheat seedlings in a controlled temperature room at 65° F. to 75° F. Mildew spores were shaken from the culture plants onto Pennol wheat seedlings which had been sprayed previously with the fungicide compound. The inoculated seedlings were kept in a controlled temperature room at 65° F. to 75° F. and subirrigated. The percent disease control was rated 8 to 10 days after the inoculation.

WHEAT STEM RUST (WSR)

Puccinia graminis (f. sp. tritici Race 15B-2) was cultured on Wanzer wheat seedlings for a period of 14 days in a greenhouse. A water suspension of the spores from infested plants was obtained and the spore concentration was adjusted to about 200,000 spores per ml of deionized water. Wanzer wheat plants which had been previously treated with the fungicide compounds were inoculated by applying the stem rust spore suspension, until runoff, with a DeVilbiss atomizer at 5 lbs. per square inch air pressure. After inoculation, the plants were placed in a humid environment at approximately 75° F. where they were exposed to 12 hours of continuous darkness followed by a minimum of 3 to 4 hours of light having an intensity of about 500 footcandles. The temperature in the chamber did not exceed 85° F. At the end of the light period, the plants were placed in a greenhouse where they were permitted to grow for a period of two weeks at which time the percent disease control was determined.

WHEAT LEAF RUST (WLR)

Puccinia recondita (f. sp. tritici Races PKB and PLD) was cultured on seven day old wheat (cultivar Fielder) over a 14 day period in the greenhouse. Spores were collected from the leaves with a cyclone vacuum or by settling on aluminum foil. The spores were cleaned by sieving through a 250 micron opening screen and stored or used fresh. Storage employed sealed bags in an Ultralow freezer. When stored, spores must be heat shocked for two minutes at 40° F. before use. A spore suspension is prepared from dry uredia by adding 20 mg (9.5 million) per ml of Soltrol oil. The suspension is dispensed into gelatin capsules (0.7 ml capacity) which attach to the oil atomizers. One capsule is used per flat of twenty of the two inch square pots of seven day old Fielder wheat. After waiting for at least 15 minutes for the oil to evaporate from the wheat leaves, the plants are placed in a dark mist chamber (18°-20° C. and 100% relative humidity) for 24 hours. The plants are then put in the greenhouse for the latent period and scored after 10 days for disease levels. Protective and curative tests were inoculated one day after and two days, respectively, before spraying the plants with the test chemicals.

                                      TABLE 8                                      __________________________________________________________________________     % Control* vs. Assorted Fungi                                                  Example                                                                             CDM  RB  RSB  TLB WPM  WSR WLR                                            __________________________________________________________________________     1    100/200                                                                             80/200                                                                             0/300                                                                               90/300                                                                             0/300                                                                               70/300                                                                             --/--                                          2    70/300                                                                               0/300                                                                             0/300                                                                                0/300                                                                             0/300                                                                               40/300                                                                             --/--                                          3    90/200                                                                              94/200                                                                             0/300                                                                               20/300                                                                             0/300                                                                               40/300                                                                             --/--                                          4    95/300                                                                              89/200                                                                             0/300                                                                               15/300                                                                             0/300                                                                               30/300                                                                             --/--                                          5    49/100                                                                              50/100                                                                             **   35/100                                                                             0/300                                                                               50/100                                                                             --/--                                          6    85/100                                                                              50/100                                                                             0/100                                                                                0/100                                                                             0/100                                                                               --/--                                                                               50/100                                        7     0/100                                                                              50/100                                                                             0/100                                                                                0/100                                                                             60/100                                                                              --/--                                                                               50/100                                        __________________________________________________________________________      *Values Given as % Control/Ppm Application Rate                                **Test did not replicate                                                       --/-- = test not run                                                     

While the invention has been described in sufficient detail for those skilled in the art to be able to make and use it, various alternatives, modifications, and improvements should become apparent from the forgoing disclosure without departing from the spirit and scope of the invention. 

I claim:
 1. A compound of the formula ##STR17## wherein R₁ is selected from phenyl, phenethyl and benzyl, each optionally substituted with chloro or C₁ -C₄ -alkyl,Q is ##STR18## and Z₁ and Z₂ are independently selected from hydrogen, halogen and (C₁ -C₄) alkyl.
 2. Compound of claim 1 wherein Z₁ is halo.
 3. Compound of claim 1 wherein Z₁ is chloro and Z₂ is methyl.
 4. Compound of claim 1 wherein R₁ is selected from phenyl and 4-chlorophenyl.
 5. Compound of claim 2 wherein R₁ is selected from phenyl and 4-chlorophenyl.
 6. Compound of claim 3 wherein R₁ is selected from phenyl and 4-chlorophenyl.
 7. A composition comprising a compound of claim 1 in a fungicidally-effective amount and in an agronomically acceptable carrier. 